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Polymer microfluidic systems for samplepreparation for bacterial detection
KTH, School of Electrical Engineering (EES), Micro and Nanosystems.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Sepsis, caused by blood stream infection, is a very serious health condition thatrequires immediate treatment using antibiotics to increase the chances for patientsurvival. A high prevalence of antibiotic resistance among infected patients requiresstrong and toxic antibiotics to ensure effective treatment. A rapid diagnostic devicefor detection of antibiotic resistance genes in pathogens in patient blood would enablean early change to accurate and less toxic antibiotics. Although there is a pressingneed for such devices, rapid diagnostic tests for sepsis do not yet exist.In this thesis, novel advances in microfabrication and lab-on-a-chip devices arepresented. The overall goal is to develop microfluidics and lab-on-a-chip systems forrapid sepsis diagnostics. To approach this goal, novel manufacturing techniques formicrofluidics systems and novel lab-on-a-chip devices for sample preparation havebeen developed.Two key problems for analysis of blood stream infection samples are that lowconcentrations of bacteria are typically present in the blood, and that separation ofbacteria from blood cells is difficult. To ensure that a sufficient amount of bacteria isextracted, large sample volumes need to be processed, and bacteria need to be isolatedwith high efficiency. In this thesis, a particle filter based on inertial microfluidicsenabling high processing flow rates and integration with up- and downstream processesis presented.Another important function for diagnostic lab-on-a-chip devices is DNA amplificationusing polymerase chain reaction (PCR). A common source of failure for PCRon-chip is the formation of bubbles during the analysis. In this thesis, a PCR-on-chipsystem with active degassing enabling fast bubble removal through a semipermeablemembrane is presented.Several novel microfabrication methods were developed. Novel fabrication techniquesusing the polymer PDMS that enable manufacturing of complex lab-on-a-chipdevices containing 3D fluidic networks and fragile structures are presented. Also,a mechanism leading to increased accuracy in photopatterning in thiol-enes, whichenables rapid prototyping of microfluidic devices, is described. Finally, a novel flexibleand gas-tight polymer formulation for microfabrication is presented: rubbery OSTE+.Together, the described achievements lead to improved manufacturing methodsand performances of lab-on-a-chip devices, and may facilitate future development ofdiagnostic devices.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2014. , xiv, 65 p.
Series
TRITA-EE, ISSN 1653-5146 ; 2014:038
National Category
Engineering and Technology
Identifiers
URN: urn:nbn:se:kth:diva-151244ISBN: 978-91-7595-244-4 (print)OAI: oai:DiVA.org:kth-151244DiVA: diva2:747137
Public defence
2014-10-03, FR4 (Oskar Klein-auditoriet), Roslagstullsbacken 21, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

QC 20140916

Available from: 2014-09-17 Created: 2014-09-15 Last updated: 2014-09-19Bibliographically approved
List of papers
1. Fabrication and transfer of fragile 3D PDMS microstructures
Open this publication in new window or tab >>Fabrication and transfer of fragile 3D PDMS microstructures
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2012 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 22, no 8, 1-9 p.Article in journal (Refereed) Published
Abstract [en]

We present a method for PDMS microfabrication of fragile membranes and 3D fluidic networks, using a surface modified water-dissolvable release material, poly(vinyl alcohol), as a tool for handling, transfer and release of fragile polymer microstructures. The method is well suited for the fabrication of complex multilayer microfluidic devices, here shown for a PDMS device with a thin gas permeable membrane and closely spaced holes for vertical interlayer connections fabricated in a single layer. To the authors knowledge, this constitutes the most advanced PDMS fabrication method for the combination of thin, fragile structures and 3D fluidics networks, and hence a considerable step in the direction of making PDMS fabrication of complex microfluidic devices a routine endeavour.

Keyword
Microfluidic Devices, Layer
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-95357 (URN)10.1088/0960-1317/22/8/085009 (DOI)000306649000009 ()2-s2.0-84864447006 (Scopus ID)
Note

QC 20150624

Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-12-07Bibliographically approved
2. Low-stress transfer bonding using floatation
Open this publication in new window or tab >>Low-stress transfer bonding using floatation
2012 (English)In: Journal of Micromechanics and Microengineering, ISSN 0960-1317, E-ISSN 1361-6439, Vol. 22, no 7, 075005-075011 p.Article in journal (Refereed) Published
Abstract [en]

A novel method for transferring thin, large-area polymer layers from a mould and its subsequent bonding to a destination substrate is presented here. Buoyancy is used for transfer via floatation to allow the release of internal stress in the polymer and to avoid induced strain. Additionally, floatation leads to wrinkle-free contact between the polymer layer and its destination substrate, an important feature for the transfer of large-area polymer sheets. Poly(vinyl alcohol) is used as a release film on the mould, from which the device polymer layer is released using ultrasonication. The polymer layer floats from the mould to a destination surface, to which it automatically aligns. Here, the method is demonstrated by the successful manufacturing of a 4 '' sized, triple microfluidic layer PDMS stack on a silicon wafer, containing a total of 48 large-area, fragile membranes, each with a thickness of 50 mu m.

Place, publisher, year, edition, pages
Institute of Physics Publishing (IOPP), 2012
Keyword
poly(dimethylsiloxane), PDMS, transfer bonding, stress release, membrane, poly(vinyl alcohol), PVA, release layer, microfabrication, MEMS, soft lithography, microfluidics, lab-on-chip
National Category
Electrical Engineering, Electronic Engineering, Information Engineering
Identifiers
urn:nbn:se:kth:diva-95362 (URN)10.1088/0960-1317/22/7/075005 (DOI)000305890600019 ()2-s2.0-84863815943 (Scopus ID)
Funder
EU, European Research Council
Note

QC 20120730

Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-12-07Bibliographically approved
3. Leak-tight vertical membrane microvalves in PDMS enabled by a novel 3D manufacturing process
Open this publication in new window or tab >>Leak-tight vertical membrane microvalves in PDMS enabled by a novel 3D manufacturing process
(English)Manuscript (preprint) (Other academic)
National Category
Engineering and Technology
Identifiers
urn:nbn:se:kth:diva-151243 (URN)
Note

QS 2014

Available from: 2014-09-15 Created: 2014-09-15 Last updated: 2014-09-17Bibliographically approved
4. Off-Stoichiometry Improves Photostructuring of Thiol-Enes Through Diffusion-Induced Monomer Depletion
Open this publication in new window or tab >>Off-Stoichiometry Improves Photostructuring of Thiol-Enes Through Diffusion-Induced Monomer Depletion
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2016 (English)In: Microsystems and Nanoengineering, ISSN 2055-7434, Vol. 2, 15043Article in journal (Refereed) Published
Abstract [en]

Thiol-enes are a group of alternating copolymers with highly ordered networks used in a wide range of applications. Here, “click” chemistry photostructuring in off-stoichiometric thiol-enes is shown to induce microscale polymeric compositional gradients due to species diffusion between non-illuminated and illuminated regions, creating two narrow zones with distinct composition on either side of the photomask feature boundary: a densely cross-linked zone in the illuminated region and a zone with an unpolymerized highly off-stoichiometric monomer composition in the non-illuminated region. By the use of confocal Raman microscopy, it is here explained how species diffusion causes such intricate compositional gradients in the polymer, and how off-stoichiometry results in improved image transfer accuracy in thiol-ene photostructuring. Furthermore, increasing the functional group off-stoichiometry and decreasing photomask feature size is shown to amplify the induced gradients, which potentially leads to a new methodology for microstructuring.

Place, publisher, year, edition, pages
Nature Publishing Group, 2016
Keyword
thiol-ene, oste, OSTEmer, polymer, photopatterning, photolithography, monomer diffusion, click chemistry, Raman confocal microscopy, microfluidics
National Category
Nano Technology Textile, Rubber and Polymeric Materials
Research subject
Electrical Engineering; Materials Science and Engineering
Identifiers
urn:nbn:se:kth:diva-144992 (URN)10.1038/micronano.2015.43 (DOI)
Note

Updated from accepted to published.

QC 20160216

Available from: 2014-05-05 Created: 2014-05-05 Last updated: 2017-10-02
5. Rapid mold-free manufacturing of microfluidic devices with robust and spatially directed surface modifications
Open this publication in new window or tab >>Rapid mold-free manufacturing of microfluidic devices with robust and spatially directed surface modifications
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2014 (English)In: Microfluidics and Nanofluidics, ISSN 1613-4982, E-ISSN 1613-4990, Vol. 17, no 4, 773-779 p.Article in journal (Refereed) Published
Abstract [en]

A new method that allows for mold-free, rapid and easy-to-use proto- typing of micro uidic devices comprising channels, access holes and surface modied patterns, is presented. The innovative method is based on direct photolithographic patterning of an o-stoichiometry thiol-ene (OSTE) polymer formulation, tailor-made for photolithography, which oers unprecedented spatial resolution and allow for ecient, robust and reliable, room temperature surface modication and glue-free, covalent room temperature bonding. This mold-free process does not require cleanroom equipment and therefore allows for rapid, i.e. less than one hour, design-fabricate-test cycles, using a material suited for larger scale production. The excellent photolithographic properties of this new OSTE formulation allow for high-resolution patterning in hundreds of micrometers thick layers, 200 m thick in this work. Moreover, we demonstrate robust (covalent) and spatially controlled modication of the microchannel surfaces with a contact angle of 76 degrees to hydrophobic/hydrophilic areas with contact angles of 102 and 43 degrees, respectively.

Place, publisher, year, edition, pages
Springer Berlin/Heidelberg, 2014
Keyword
lab-on-chip, microfluidics, photolithography, OSTE polymer, surface modi, oste, oste+, OSTEmer, lab-on-chip, off-stoichiometric thiol-ene
National Category
Nano Technology
Research subject
Biotechnology; Materials Science and Engineering
Identifiers
urn:nbn:se:kth:diva-124363 (URN)10.1007/s10404-014-1351-9 (DOI)000342454400016 ()2-s2.0-84920255161 (Scopus ID)
Projects
Rappid
Note

QC 20141027

Available from: 2013-06-29 Created: 2013-06-29 Last updated: 2017-12-06Bibliographically approved
6. Low gas permeable and non-absorbent rubbery OSTE+ for pneumatic microvalves
Open this publication in new window or tab >>Low gas permeable and non-absorbent rubbery OSTE+ for pneumatic microvalves
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2014 (English)In: Proceedings of the 27th IEEE International Conference on Micro Electro Mechanical Systems (MEMS 2014), IEEE conference proceedings, 2014, 987-990 p.Conference paper, Published paper (Refereed)
Abstract [en]

In this paper we introduce a new polymer for use in microfluidic applications, based on the off-stoichiometric thiol–ene-epoxy (OSTE+) polymer system, but with rubbery properties. We characterize and benchmark the new polymer against PDMS. We demonstrate that Rubbery OSTE+: has more than 90% lower permeability to gases compared to PDMS, has little to no absorption of dissolved molecules, can be layer bonded in room temperature without the need for adhesives or plasma treatment, can be structured by standard micro-molding manufacturing, and shows similar performance as PDMS for pneumatic microvalves, albeit allowing handling of larger pressure. 

Place, publisher, year, edition, pages
IEEE conference proceedings, 2014
Keyword
lab-on-chip, microfluidics, microvalve, OSTE+
National Category
Textile, Rubber and Polymeric Materials
Identifiers
urn:nbn:se:kth:diva-141690 (URN)10.1109/MEMSYS.2014.6765809 (DOI)000352217500245 ()2-s2.0-84898951170 (Scopus ID)978-1-4799-3509-3 (ISBN)
Conference
The 27th IEEE International Conference on Micro Electro Mechanical Systems (MEMS 2014), January 26-30, 2014,San Fransisco, CA, USA
Funder
EU, FP7, Seventh Framework Programme
Note

QC 20140221

Available from: 2014-02-20 Created: 2014-02-20 Last updated: 2016-01-22Bibliographically approved
7. Inertial microfluidics in parallel channels for high-throughput applications
Open this publication in new window or tab >>Inertial microfluidics in parallel channels for high-throughput applications
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2012 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 12, no 22, 4644-4650 p.Article in journal (Refereed) Published
Abstract [en]

Passive particle focusing based on inertial microfluidics was recently introduced as a high-throughput alternative to active focusing methods that require an external force-field to manipulate particles. In this study, we introduce inertial microfluidics in flows through straight, multiple parallel channels. The scalable, single inlet and two outlet, parallel channel system is enabled by a novel, high-density 3D PDMS microchannel manufacturing technology, mediated via a targeted inhibition of PDMS polymerization. Using single channels, we first demonstrate how randomly distributed particles can be focused into the centre position of the channel in flows through low aspect ratio channels and can be effectively fractionated. As a proof of principle, continuous focusing and filtration of 10 μm particles from a suspension mixture using 4- and 16-parallel-channel devices with a single inlet and two outlets are demonstrated. A filtration efficiency of 95-97% was achieved at throughputs several orders of magnitude higher than previously shown for flows through straight channels. The scalable and low-footprint focusing device requiring neither external force fields nor mechanical parts to operate is readily applicable for high-throughput focusing and filtration applications as a stand-alone device or integrated with lab-on-a-chip systems.

Place, publisher, year, edition, pages
Royal Society of Chemistry, 2012
Keyword
article, filtration, force, fractionation, inertial microfluidics, lab on a chip, microfluidics, priority journal
National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:kth:diva-95364 (URN)10.1039/c2lc40241f (DOI)000310865200008 ()2-s2.0-84867518462 (Scopus ID)
Funder
Science for Life Laboratory - a national resource center for high-throughput molecular bioscienceEU, European Research Council
Note

QC 20121115. Updated from accepted to published.

Available from: 2012-05-23 Created: 2012-05-23 Last updated: 2017-12-07Bibliographically approved
8. Active liquid degassing in microfluidic systems
Open this publication in new window or tab >>Active liquid degassing in microfluidic systems
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2013 (English)In: Lab on a Chip, ISSN 1473-0197, E-ISSN 1473-0189, Vol. 13, no 22, 4366-4373 p.Article in journal, Editorial material (Refereed) Published
Abstract [en]

We present a method for efficient air bubble removal in microfluidic applications. Air bubbles are extracted from a liquid chamber into a vacuum chamber through a semipermeable membrane, consisting of PDMS coated with amorphous Teflon (R) AF 1600. Whereas air is efficiently extracted through the membrane, water loss is greatly reduced by the Teflon even at elevated temperatures. We present the water loss and permeability change with the amount of added Teflon AF to the membrane. Also, we demonstrate bubble-free, multiplex DNA amplification using PCR in a PDMS microfluidic device.

Place, publisher, year, edition, pages
RSC Publishing, 2013
Keyword
Air Bubble Formation, Pcr, Devices, Chip, Channels, Removal, Valves, Trap, Flow
National Category
Biological Sciences
Identifiers
urn:nbn:se:kth:diva-125061 (URN)10.1039/c3lc50778e (DOI)000325946800014 ()2-s2.0-84886056493 (Scopus ID)
Funder
EU, FP7, Seventh Framework Programme
Note

QC 20131114

Available from: 2013-08-06 Created: 2013-08-06 Last updated: 2017-12-06Bibliographically approved

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